Inflammation is a common and frequently-occurring disease that endangers human health and affects the quality of human life. The most common inflammation is arthritis, and there are currently approximately 355 million patients suffering from arthritis all over the world. It is estimated that there are approximately 100 million patients suffering from arthritis in China, and this number is increasing every year. Therefore, the development of anti-inflammatory and analgesic drugs is of great significance.
Traditional non-steroidal anti-inflammatory drugs, including ibuprofen and diclofenac, are the main drugs for the treatment of arthritis. However, while exerting analgesic and anti-inflammatory effects, such drugs also bring about a variety of serious adverse reactions and complications to the digestive tract, such as epigastric discomfort, ulceration, gastrointestinal hemorrhage, perforation and intestinal obstruction, and the like.
Cyclooxygenase (COX) is a major target for non-steroidal anti-inflammatory drugs. COX has two isomers, i.e., COX-1 and COX-2. Although the two isomers have 60% homology in structure, they have different distributions in tissue cells and different biological functions. COX-1 exists in normal tissues, catalyzes the synthesis of PGE2 and PGI2, and has functions of cell stabilization and cytoprotection, whereas COX-2 is cytokine-inducible and it only exists in damaged tissues. The prostaglandin catalytically synthesized by COX-2 is proinflammatory and has an inflammatory and pain-causing effect. It is believed by most scholars that traditional non-steroidal anti-inflammatory drugs inhibit both COX-1 and COX-2, and inhibition of COX-1 leads to a variety of serious adverse reactions and complications in digestive tract. Therefore, searching for inhibitors that selectively inhibit COX-2 has become the main direction of research and development.
Coxib non-steroidal anti-inflammatory drugs such as celecoxib, rofecoxib, and valdecoxib are representatives of this type of selective inhibitors for COX-2. They can selectively inhibit COX-2 without acting on COX-1, minimizing the intestinal side effects while exerting their anti-inflammatory effects. However, they also have deficiencies, for example, it has been identified that rofecoxib will cause cardiovascular risk, therefore it has been withdrawn globally. Celecoxib is also required to be used with caution due to the presence of cardiovascular risk in some patients.
Although the cardiovascular risk of coxib drugs has an impact on COX-2 inhibitory non-steroidal anti-inflammatory drugs, most studies have suggested that for COX-2 inhibitory drugs, since their chemical structures are different, their safeties are completely different. Some COX-2 inhibitory drugs even have a potential protective effect on angiocarpy. Currently, there are approximately hundreds of millions of people taking non-steroidal anti-inflammatory drugs worldwide, and COX-2 inhibitors are an important part among them. Although the COX-2 families have “bad guys” with serious adverse reactions, they have played a huge role in relieving the patient's conditions, and there is no better alternative drugs having been found yet currently. Therefore, the development of COX-2 inhibitors remains an important direction for anti-inflammatory and analgesic drugs.
A sulfur pentafluoride substituted benzopyran-based compound is derived from a bisaryl heterocyclic coxib compound, has the same pharmaceutical effect and selectivity as a bisaryl heterocyclic coxib compound, i.e., has a selective inhibition effect on the COX-2 enzyme, and its structural formula is as follows:

CN104860914A discloses that sulfur pentafluoride phenol is used as a raw material for direct ortho-formylation, and then a benzopyran-based compound is substituted by sulfur pentafluoride, or after multiple steps of synthesis, the ortho position is brominated, and then ortho-formylated, thus a sulfur pentafluoride substituted benzopyran-based compound and a chiral compound thereof are synthesized, it also discloses the synthetic routes of the following sulfur pentafluoride substituted benzopyran-based compounds:

The difficulty in the synthesis of such compounds is that there are very few sulfur pentafluoride phenol-based compounds with substituents in other positions which can satisfy the synthesis conditions and are available. Currently, only sulfur pentafluoride phenol can satisfy the synthesis conditions and is available. The sulfur pentafluoride phenol is needed to be structured to synthesize novel sulfur pentafluoride phenols with multiple substituent groups, thereby sulfur pentafluoride salicylaldehyde with multiple substituent groups can be obtained. Finally, a sulfur pentafluoride substituted benzopyran-based compound and a chiral structure thereof can be synthesized on this basis.
Therefore, there is still a need in the art to develop a synthetic method for a sulfur pentafluoride substituted benzopyran-based compound.